Induction therapies in live donor kidney transplantation on tacrolimus and mycophenolate with or without steroid maintenance

Bekir Tanriover, Song Zhang, Malcolm MacConmara, Ang Gao, Burhaneddin Sandikci, Mehmet U S Ayvaci, Mutlu Mete, Demetra Tsapepas, Nilum Rajora, Prince Mohan, Ronak Lakhia, Christopher Y. Lu, Miguel Vazquez

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background and objectives: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. Design, setting, participants, & measurements: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. Results: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. Conclusions: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

Original languageEnglish (US)
Pages (from-to)1041-1049
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number6
DOIs
StatePublished - 2015

Fingerprint

Tacrolimus
Kidney Transplantation
Interleukin-2
Steroids
Maintenance
Tissue Donors
Antilymphocyte Serum
Living Donors
Confidence Intervals
Mycophenolic Acid
Rabbits
Allografts
Therapeutics
Propensity Score
Odds Ratio
Tissue and Organ Procurement
Selection Bias
Interleukin-2 Receptors
Organ Transplantation
Registries

Keywords

  • Acute allograft rejection
  • Immunosuppression
  • Kidney transplantation

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

Induction therapies in live donor kidney transplantation on tacrolimus and mycophenolate with or without steroid maintenance. / Tanriover, Bekir; Zhang, Song; MacConmara, Malcolm; Gao, Ang; Sandikci, Burhaneddin; Ayvaci, Mehmet U S; Mete, Mutlu; Tsapepas, Demetra; Rajora, Nilum; Mohan, Prince; Lakhia, Ronak; Lu, Christopher Y.; Vazquez, Miguel.

In: Clinical Journal of the American Society of Nephrology, Vol. 10, No. 6, 2015, p. 1041-1049.

Research output: Contribution to journalArticle

@article{69d998636cc44b25869e63319395e429,
title = "Induction therapies in live donor kidney transplantation on tacrolimus and mycophenolate with or without steroid maintenance",
abstract = "Background and objectives: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. Design, setting, participants, & measurements: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. Results: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95{\%} confidence interval [95{\%} CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95{\%} CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95{\%} CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95{\%} CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95{\%} CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95{\%} CI, 0.97 to 1.45), compared with IL2-RA induction. Conclusions: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.",
keywords = "Acute allograft rejection, Immunosuppression, Kidney transplantation",
author = "Bekir Tanriover and Song Zhang and Malcolm MacConmara and Ang Gao and Burhaneddin Sandikci and Ayvaci, {Mehmet U S} and Mutlu Mete and Demetra Tsapepas and Nilum Rajora and Prince Mohan and Ronak Lakhia and Lu, {Christopher Y.} and Miguel Vazquez",
year = "2015",
doi = "10.2215/CJN.08710814",
language = "English (US)",
volume = "10",
pages = "1041--1049",
journal = "Clinical Journal of the American Society of Nephrology",
issn = "1555-9041",
publisher = "American Society of Nephrology",
number = "6",

}

TY - JOUR

T1 - Induction therapies in live donor kidney transplantation on tacrolimus and mycophenolate with or without steroid maintenance

AU - Tanriover, Bekir

AU - Zhang, Song

AU - MacConmara, Malcolm

AU - Gao, Ang

AU - Sandikci, Burhaneddin

AU - Ayvaci, Mehmet U S

AU - Mete, Mutlu

AU - Tsapepas, Demetra

AU - Rajora, Nilum

AU - Mohan, Prince

AU - Lakhia, Ronak

AU - Lu, Christopher Y.

AU - Vazquez, Miguel

PY - 2015

Y1 - 2015

N2 - Background and objectives: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. Design, setting, participants, & measurements: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. Results: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. Conclusions: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

AB - Background and objectives: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. Design, setting, participants, & measurements: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. Results: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. Conclusions: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

KW - Acute allograft rejection

KW - Immunosuppression

KW - Kidney transplantation

UR - http://www.scopus.com/inward/record.url?scp=84930419762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930419762&partnerID=8YFLogxK

U2 - 10.2215/CJN.08710814

DO - 10.2215/CJN.08710814

M3 - Article

C2 - 25979971

AN - SCOPUS:84930419762

VL - 10

SP - 1041

EP - 1049

JO - Clinical Journal of the American Society of Nephrology

JF - Clinical Journal of the American Society of Nephrology

SN - 1555-9041

IS - 6

ER -